This project will focus on the development of a novel redox iron chelator system for the removal of iron from diferric transferrin. These systems will have more than a simple thermodynamic iron binding advantage over transferrin. They are designed to mobilize the transferrin iron by first reducing it from Fe(III) to Fe(II) in a fast step, then to chelate the Fe(II) and promote its back oxidation to Fe(III). Based on previous model systems we expect the formation constant for the final Fe(III) complex to be around 10 to the forty, in excess of 10 to the fifteen times tighter than transferrin iron binding. Based on kinetic studies of model systems the iron should be released from the transferrin thousands of times faster than in the absence of the reduction step. The two outstanding functional pieces of these systems will be their thioglycolate-like appendayes for the reduction of the transferrin's Fe(III) to Fe(II) and their tricatecholamide spermidine backbones. We will measure how effectively these compounds remove iron from transferrin, evaluate their toxicity and their ability to remove iron from iron overloaded rats. Should this new concept prove useful, the system will be considered as a device for use in iron chelation therapy in the treatment of primary and particularly secondary hemochromatosis, e.g., Cooley's anemia.